Morphine
what is the dose of morphine and ideal pain to treat with morphine IM/IV
1-10 mg
*varies on patient tolerance
* works best on dull achy pain from visceral and skeletal muscles over sharp intermittent pain
uses
agonists site
12.5 mg postop shivering
Intrathecal and IM
doses of fentanyl
analagesia = 1-2 mcg/kg
induction= 1.5-3 mcg/kg
adjunct to VA = 2-20 mcg/kg
surgical solo = 50-150 mcg/kg
intrathecal = 25 mcg
transmucosal = 5-20 mcg/kg 45 min prior
transdermal = 75-100 mcg (18hr steady state)
dose of sufantenil
analgesia 0.1-0.4 mcg/kg
induction 18.9 mcg/kg
intraop 0.3-1 mcg/kg
infusion 0.5-1 mcg/kg
dose of alfentanil
induction laryngoscopy - 15-30 mcg/kg
induction 150-300 mcg/kg
maintenance with inhaled anesthetics 25- 150 mcg/kg/hr
what are the pharmacokinetics of morphine
IM/IV onset = 10- 20 minutes
IM peak= 45-90 min
IV peak = 15-30 min
Duration = 4-5 hrs
PO heaptic 1st pass = 25%
accumulation in kidney/liver and lungs
pharmacokinetics of mepiridine
duration 2-4 hrs
hepatic 1st pass = 80%
elimination time = 3-5 hrs
protein bound = 60% *elderly consideration
hepatic metabolism = 90%
blood brain site equillibration = 6.4 minutes
lung 1st pass = 75%
Vd= large
* IV < 80% is gone
highly vascular tissue, inactive tissue sites
Context sensitive half time is greater than sufentanil
*no change in elderly/hepatic cirrohsis
pharmacokinetics of sufantenil
small Vd
Alpha 1- acid glycoprotein
Context sensitive half time < fentanyl
rapid wake up
pharmacokinetcs of alfentanil
onset 1.4 min> fentanyl and sufentanil
cirrhosis prolongs E1/2 time
90% non-ioninzed at normal pH - low lipid soluble
higher protein binding than sufentanil
what is the metabolism and excretion of morphine
glucruonic acid conjugation
* Morphine 3- glucuronide = inactive (75-95%)
* morphine 6- glucuronide = active
renal excretion
*prolonged ventilatory depression in renal failure
E1/2 time longer with Morphine-3-glucruronide with renal dysfunction
metabolism and excretion of mepridine
90% hepatic metabolism
*normepridine
renal excretion - acidic urine accelerates excretion
metabolism and excretion of fentanyl
CYP3A - hepatic metabolism -> norfentanyl
excreted via kidneys
sufentanil metabolism and excretion
hepatic metabolism
renal and fecal excretion
*caution with renal failure
metabolism of alfentanil
CYP3A4 -> noralfentanil
what are the side effects of morphine
decreases SNS tone in veins; decrease venous return, BP, CO -> orthostatic Hypotension, syncope
bradycardia + histamine release -> decreased BP
opioid+ N2O + benzo = decreased CO/BP
dose-dependent ventilation depression
increased PaCO2 -> shifts curve to the right
minute ventilation is maintained (increased TV with decreased RR)
urinary urgency
flushing from histamine release on face, neck, chest
side effects of mepridine
Tachycardia, mydriasis, dry mouth, serotonin syndrome (MAOIs and TCAs), negative inotrope, impaired ventilation, crosses the placenta
toxicity- delirium, myoclonus, seizures
side effects of fenatnyl
large doses cause depressed carotid receptor reflex
seizure-like activity
SSEP & EEG with doses >30 mcg/kg
increase ICP 6-9 mmHg
side effects of sufentanil
bradycardia -> decreased CO
rigidity of chest wall and abdominal muscles
tx= physostigmine
side effect of alfentanil
chest wall rigidity -> acute dystonia in Parkinson's
odds and evens of morphine
crosses the palcenta -> neonate depression
physostigmine reverses respiratory depression without removing analgesia
increases sphincter pressure 53% (sphincter of Oddi) -> relieved with Glucagon 2 mg (incrementally)
morphine tolerance at 25 days
odds and evens of mepiridine
structurally similar to atropine and lidocaine
Withdrawal symptoms develop more rapidly
spasm of sphincter of Oddi (increases by 61%)
Mother to fentanyl, remi, al, Remi
odd and evens of fentanyl
syngerism with propofol and benzos
spasm of sphincter of oddi (99%)
metabolism and excretion of remifentanil
hydrolysis of hepatic enzymes, plasma, and tissue esterases
excretion via kidneys
*unchanged with renal and liver disease
side effects of remifentanil
seizure-like activity
N/V
depression of ventilation
decreased BP and HR
hyperalgesia - previous acute exposure to large opioid doses/tolerance